Screeing of novel microbial- and enzyme catalysts for expeditious chemical synthesis of useful substances

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Based on the chemo-enzymatic synthesis with complementary use of organic synthesis and enzyme-catalyzed transformation, the following researches were accomplished.1) Screening of microorganisms which can reduce sterically hindered ketones. in enantifacially selective mannerTowards the synthesis of sterically hindered optically active secondary alcohol, yeast strains (Candida floricola IAM 13115 and)-Trichosporon cutaneum IAM 12206) with si-face hydride attack on isopropyl phenylsulfonylmethyl ketone were newly developed by screening. Strains with complementary re-facial selectivity (Pichia angusta IAM 12895 and Pichia minute IAM 12215) were also found. Based on the substrate specificity studies of these four strains, microbial reduction was applied to the synthesis of (3S, 5S)-2, 6-dimethyl-3, 5-heptanediol.2) Application of newly found yeast strains for the synthesis of naturally occurring bioactive product, such as modiolide A.While the first total synthesis of modiolide A, a ten-membered ring lactone with a marine-origin was achieved, an important chiral building block for constructing the chirality at C-4, (S)-6-[(4-methoxybenzyl)oxy]-1-trimethylsilyl-1-hexyn-3-ol was obtained in as high as 96.1% ee. Asymmetric reduction of a silylated propargyl ketone mediated by whole-cell of Pichia minute IAM 12215 was established.3) Delopment of Bacillus subtilis epoxide hydrolase in organic syntheses.An expeditious route for the enantiopure 2-methylpropane-1, 2, 3-triol monobenzyl ether was examined. An engineered Bacillus subtilis epoxide hydrolase worked enantioselectively on a racemic epoxide to provide the desired product in highly enantiomerically enriched state.